Caffeic Acid Regulates High Glucose-Induced Inflammatory Responses in BV-2 Microglial Cells: Implications for Purinergic Signaling

High glucose-induced microglial activation contributes to inflammatory processes associated with diabetic complications. Thus, the effects of caffeic acid (CA) on inflammatory responses and purinergic signaling parameters in high glucose-challenged BV-2 microglial cells were investigated. A) Oxidative stress; b) Enzymatic activities of Ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), Ecto-5-nucleotidase (E-5'-NT), and Adenosine deaminase (ADA); c) Density of P2X7R, A1R, and A2AR purinoceptors; d) Inflammatory markers (IBA-1, NLRP3, and IL-1β); and e) Apoptosis and cell cycle were assessed. Treatment with CA (50 and 75 µM, 24 h) in cells exposed to high glucose medium (GL 25 mM, 48 h) increased viability and reduced nitric oxide (NO), reactive species (RS), and thiobarbituric acid reactive substances (TBARS) levels compared to high glucose-challenged cells. CA also restored ATP and ADP hydrolysis and reduced ADA activity. Furthermore, CA increased the density of the A1R while reversing the high glucose-induced increase in P2X7R and A2AR densities. Moreover, CA treatment attenuated the increase in IL-1β density in high glucose medium, whereas only CA (75 µM) treatment reduced NLRP3 and IBA-1 densities. Besides, this phenolic compound decreased apoptosis and promoted cell cycle progression by increasing the proportion of cells in the S and G2/M phases. Overall, findings suggest that CA attenuates high glucose-induced inflammatory and oxidative alterations in BV-2 microglial cells, besides modulating purinergic enzyme activities and purinoceptor density. These results support the potential involvement of purinergic signaling in the cellular effects of CA and provide possible mechanistic insights into its antioxidant and anti-inflammatory actions under high glucose conditions.